Neurotransmitters: Electrical and Chemical Synapses PDF

Electrical synapse Electrical synapses, are characterized by direct open fluid channels that conduct electricity from one cell to the next. Most of these consist of small protein tubular structures called gap junctions that allow FREE movement of ions from the...

Electrical synapse Electrical synapses, are characterized by direct open fluid channels that conduct electricity from one cell to the next. Most of these consist of small protein tubular structures called gap junctions that allow FREE movement of ions from the interior of one cell to the interior of the next. transmitted from one smooth muscle fiber to the next in visceral smooth muscle and from one cardiac muscle cell to the next in cardiac muscle cell ALLOWS SIGNALS TRANSMISSION IN EITHER DIRECTION Chemical synapse chemical synapse: one way conduction – directed towards a specific goal (highly focused) – “PRINCIPLE OF ONE WAY CONDUCTION” From presynaptic neuron that secretes the NTM and the postsynaptic neuron where the NTM acts Important NTMs (>40 NTMs found in humans): acetylcholine, norepinephrine, epinephrine, histamine, gamma-aminobutyric acid (GABA), glycine, serotonin, and glutamate. Neurotransmitters (NTM) a neurotransmitter (or often called simply transmitter substance) One way conduction: highly focused function: sensory, motor, memory, emotions, etc. Binds to receptor proteins at the post synaptic neuron Action of the Transmitter Substance on the Postsynaptic Neuron Function of “RECEPTOR PROTEINS” Cation (Na⁺ mainly, K⁺,Ca⁺⁺) Ion channel Postsynaptic 8 Ionophore component (in) Second messenger activator Anion (Cl⁻) receptor (molecule) = Binding component (out) Bind to NTM in synaptic cleft  Receptors on Effector organs: Excitation or inhibition of the effector cell by changing its membrane permeability Opening or closing of Ca++ channel Influx of Na+ depolarizes the membrane, causing cell excitation K+ channels at times open and causes K+ ions to diffuse out of cell causing hypernegativity, causing cell inhibition  Receptors on Effector organs: Receptor action by intracellular alteration via “second messenger” enzymes SM enzymes usually connected to the receptor protein protruding into the interior of the cell i.e., NE binding to its receptors outside the cell will cause increased activity of enzyme adenyl cyclase on inside of the cell Adeny cyclase then forms cAMP cAMP then initiates various intracellular actions depending on type of effector cell and chemical make up I. Binding component protrudes outward from the membrane into the synaptic cleft—here it binds the neurotransmitter coming from the presynaptic terminal IIa. Ionophore: Ion channel Cation channels lined with negative charges These negative attracts cations that are positively charged: usually Na+ and sometimes K+ and Ca++… AND repels negative charges such as Cl- preventing its passage When channels open and becomes large enough, it allows N+ ions to enter, causing excitation A NTM that opens cation channels are called an excitatory transmitter. IIa. Ionophore: Ion channel Anion channels lined with positive charges attracts anions that are negatively charged that allow mainly Cl- ions to pass and some minute quantities of other anions. Repels positive ions Positive ions also unable to pass because they are too large to pass when hydrated When channels open,. Negative electrical charges enter making the inside of the cell negative. Therefore transmitter substance that open these channels are called inhibitory transmitters.  Excitatory or Inhibitory Receptors in the Postsynaptic Membrane Excitation (+charge intracellular) Inhibitory (-charge intracellular) Open Cl⁻ channel (↑influx of Cl⁻ Open Na⁺ channel (↑inflow to in postsynaptic) postsynaptic) Most common Depressed conduction to chloride through Cl channel (↓Cl⁻ inflow) ↑k⁺ conductane out of the postsynaptic neuron Depressed conduction to K (↓k⁺ diffusion outside ) Activation of cellular receptor Internal metabolism changes the # of enzymes that inhibit metabolic excitation or inhibition functions NTM activation of an ion channel Opens channel within a fraction of a millisecond When NTM no longer present, channel closes rapidly Opening and close of these channels allow for rapid control of postsynaptic neurons IIb. Ionophore: Second Messenger system in the post synaptic neuron Causes the prolonged effect needed by the nervous system in some occasions. Example, process of memory, requires prolonged changes in neurons even after the initial NTM substance is gone (The ion channel system not appropriate for some functions as these channels close within milliseconds after the disappearance of NTM substance) 2 types of NTM receptors Ionotropic Receptors Metabotropic Receptors 2 TYPES OF NTM RECEPTORS (a) Ionotropic receptors ligand gated ion channel ionotropic receptors Ligand: an ion or molecule that binds to another, i.e., NTM Membrane channels open or close in response to the binding of a chemical messenger Ligand regulates the ion channel and usually selective to one or more ions such as Na+, K+, Ca++ or Cl- 2 TYPES OF NTM RECEPTORS: (b) Metabotropic receptors: Second messenger system: most common: G (guanine nucleotide) protein-coupled receptor When activated, a series of intracellular events are triggered causing opening of ion channels; involving various second messenger chemicals Do NOT DIRECTLY use ion channel pore When NTM binds to the receptor, an activation results via G protein, which then activates secondary messengers Takes LONGER to effect and MORE WIDESPREAD throughout cell than the ionotropic receptors Pathway for many living organisms Gene changes Smooth muscle relaxation, Higher concentration in platelet inhibition, changes in gene expression Both are able to regulate the activity of neurons, control metabolic processes, facilitate chemical and electrical signaling cascades, etc. They are also capable of activating ion channels and several protein enzymes. Neurotransmitters NEUROTRANSMITTERS (SYNAPTIC TRANSMITTERS) Small molecule Large molecule Rapidly acting Neuropeptides Acute/fast Acts more slowly responses Prolonged actions i.e., sensory and to cause long term motor responses changes in number or sizes of synapses Small molecule NTM ACETYLCHOLINE (ACH) Organic chemical found in various parts of the body esp neuromuscular junctions and ANS Parts of the body that uses acetylcholine are called CHOLINERGICS Those that interfere with ACH are called anticholinergics Acetylcholine Secreted by: (1) the terminals of the large pyramidal cells from the motor cortex, (2) basal nuclei (3) the motor neurons that innervate the skeletal muscles (4) the preganglionic neurons of the autonomic nervous system (5) the postganglionic neurons of the parasympathetic nervous system (6) some of the postganglionic neurons of the sympathetic nervous system (not common) Acetylcholine mostly excitatory effect-muscles incl GI some inhibitory effects i.e., such as inhibition of the heart by the Vagus cranial nerve. Known for its role in memory and learning Alzheimer’s Disease associated with breakdown of acetylcholine neurons ACETYLCHOLINE (ACH) Commonly binds with nicotinic and muscarinic receptors These receptors care cumulatively called cholinergic receptors ACETYLCHOLINE (ACH) Nicotinic receptors commonly found on muscle cells, CNS, ANS. Integral for movement; Ionotropic receptor Muscarinic receptors commonly found in both CNS, PNS of the heart, lungs, upper GI tract and sweat glands Metabotropic receptor use a G-protein. When ACh binds to the receptor, this special protein changes shape, which then allows it to phosphorylate various second messengers. Acetylcholine synthesis Post synapse: Acetylcholine (broken down by acetylcholinesterase) Choline and Acetate -CHOLINE transported back to the presynaptic neuron for resynthesis -ACETATE is excreted or - reused as Acetyl CoA (combination of acetate and coenzyme A molecules: important for protein, carb, lipid metabolism) Acetylcholine synthesis Post synapse: Choline in the Presynaptic neuron PLUS Acetyl CoA via acetyl transferase New ACH synthesized Norepinephrine (NE) secreted by: 1) in the brain stem and hypothalamus. 2) pons (control of overall activity and mood of the mind, i.e., wakefulness) 3) most postganglionic neurons of the sympathetic nervous system (some excitatory, some inhibitory) activates excitatory receptors, but in a few areas, it activates inhibitory receptors Norepinephrine (NE) Also called noradrenaline (NA) Binds with noradrenergic receptors Commonly binds with alpha 1,2; beta 1,2,3 receptors STRESS decreases source of adrenalin, EXERCISE increases it Associated with putting our system on “high alert” Main NTM for SNS responsible for tonic and reflexive changes in cardiovascular tone. Important role in attention and concentration Synthesis of NE and dopamine (dopamine a precursor of NE) Phenylalanine (essential amino acid) (via enzyme phenylalanine hydroxylase) Tyrosine (non essential amino acid) Hydroxylation (via enzyme tyrosine hydroxylase) L dopa (via enzyme DOPA decarboxylase, Decarboxylation conversion in the cytoplasm) Dopamine Hydroxylation (via enzyme dopamine monooxygenase, conversion occurs in NTM vesicles) Norpinephrine Epinephrine (EPI) Also known as adrenalin / adrenaline Produced by adrenal glands and some neurons. Binds with adrenergic receptors Responsible for flight or fight response (ANS) Epinephrine Adrenaline Highly responsive to metabolic or global challenges to homeostasis, such as glucoprivation, and manifestations of emotional distress. EPI Pen: Use to treat cardiac arrest, anaphylaxis, hypoglycemia, bronchospasm Epinephrine synthesis from NE (via enzyme Methylation phenylethanolamine N Methyltransferase Epinephrine Dopamine secreted by neurons that originate in the substantia nigra; the termination of these neurons is mainly in the striatal region of the basal nuclei The effect is usually inhibition. Blocks the tendency of neuron to fire. Binds with dopaminergic receptors Decreased (Parkinson’s); Increased (related to schizophrenia) Dopamine Outside of the CNS: blood vessels vasodilation by inhibiting norepinephrine release Kidneys: Increases sodium excretion and urine output; Pancreas: decreased insulin production; Digestive system: decreased gastrointestinal motility and protection of intestinal mucosa; Immune system: decreased activity of the lymphocytes  Norepinephrine degradation: Reuptake into adrenergic nerve endings via active transport, removing 50-80% of NE Diffusion away from the nerve endings into surrounding body fluids then into the blood, removing most of the remaining NE Destruction of small amounts by tissue enzymes (monoamine oxidase {MAO} found in nerve endings and catechol-O-methyl transferase, present diffusely in tissues)  Norepinephrine degradation: NE secreted directly into the tissue: only active for a few seconds (rapid reuptake and diffusion) NE and EPI secreted into the blood by adrenal medullae remain active until diffused into some tissue, destroyed by catechol o methyl transferase (mainly happens in the liver) When secreted in the blood, NE and EPI remain active for 10-30 seconds and goes into extinction over 1 to several minutes  Receptors on Effector organs: NTM binds with receptors before they can stimulate an effector organ Found outside of the cell membrane Binding of NT with receptor causes a change in the structure of the protein molecule causing an excitation nor inhibition by: Change in membrane permeability to one or more ions Activating or inactivating an enzyme attached to the other end of the receptor protein, protruding to the interior of the cell